Predictors of Mortality and Outcomes of Therapy in Low Flow Severe Aortic Stenosis: A PARTNER Trial Analysis
How did the presence of low cardiac output affect mortality outcomes among patients with severe aortic stenosis (AS) referred for transcatheter aortic valve replacement (TAVR) and enrolled in the PARTNER trial?
The PARTNER trial randomly assigned patients with severe AS to medical management versus TAVR (“inoperable” [cohort B]), and to surgical aortic valve replacement (SAVR) versus TAVR (“high risk” [cohort A]). Prospectively collected data were reviewed to determine the impact on outcomes of low flow (LF; defined as stroke volume index [SVI] ≤35 ml/m2), low left ventricular ejection fraction (LVEF; defined as <50%), and low gradient (LG; defined as mean gradient <40 mm Hg).
Among 971 patients with evaluable echocardiograms (92%); LF AS was observed in 530 (55%), LF and low EF in 225 (23%); and LF, low EF, and LG in 147 (15%). Two-year mortality was significantly higher in patients with LF compared with normal SVI (47% vs. 34%; hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.25-1.89; p = 0.006). In the inoperable cohort, patients with LF had higher mortality than those with normal flow, but both groups improved with TAVR (46% vs. 76% with LF and 38% vs. 53% with normal flow, p < 0.001). In the high-risk cohort, there was no difference between TAVR and SAVR. In patients with paradoxical LF and LG with preserved LVEF, TAVR reduced 1-year mortality from 66% to 35% (HR, 0.38; p = 0.02). LF was an independent predictor of mortality in all patient cohorts (HR, ~1.5), whereas EF and gradient were not.
The authors concluded that LF (SVI ≤35 ml/m2) is common among patients with severe AS, and independently predicts mortality. Survival is improved with TAVR compared to medical management, and similar with TAVR and SAVR. A measure of flow (SVI to body surface area) should be included in the evaluation and therapeutic decision making of patients with severe AS.
Severe AS can be defined echocardiographically by mean gradient >40 mm Hg or by effective orifice area (EOA; from the continuity equation) <1.0 cm2 (or EOA indexed to body surface area <0.6 cm2/m2). However, calculated EOA can be dramatically affected by various errors (including measurement of the LV outflow tract diameter, the assumption of a circular LV outflow tract, and the location of the LV outflow tract pulsed-wave Doppler sample volume). In clinical practice, probably most errors result in under-estimation of EOA, and most instances of discordant data regarding AS severity relate to EOA prediction of more severe AS than gradients. In such a scenario, the clinician must distinguish between LF, LG severe AS (in which the gradients are low because of a low cardiac output, sometime in the setting of normal LVEF), and measurement error. However, the stakes are clearly high in making this distinction. Patients with true LF, LG severe AS (including those with normal LVEF) are at high risk of morbid and mortal outcomes without intervention. This study nicely reinforces that true LF, LG severe AS should be recognized and treated.
Keywords: Heart Valve Prosthesis, Decision Making, Stroke Volume, Cardiac Output, Low
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